Uncommon/rare oncogenic drivers in non‐small cell lung cancer: Consensus and contention

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Yi‐Long Wu^¹

(

), Shun Lu^², Ying Cheng^³, Qing Zhou^¹

(

), Hai‐Yan Tu^¹(

), Qing‐Hua Zhou^⁴, Lv‐Hua Wang^⁵, Li Zhang^⁶, Jian‐Ying Zhou^⁷, Cheng Huang^⁸, Ming Chen^⁶, Cheng‐Ping Hu^⁹, Shao‐Kun Chuai^¹⁰, Xiao‐Nan Wang^¹¹, Xiao‐Qing Liu^¹², Ji‐Wei Liu^¹³, Peng‐Hui Zhou^⁶, Wei‐Zhi Chen^¹⁴, Ling‐Hua Yan^¹⁵, Yun‐Peng Liu^¹⁶, An‐Wen Liu^¹⁷, Xu‐Chao Zhang^¹, Hui Li^³, Rong‐Rong Chen^¹⁸, Dong‐Mei Lin^¹⁹, Cong‐Ying Xie^²⁰, Zheng‐Fei Zhu^²¹, Hui‐Ying Liang^¹, Yong Song^²², Xiao‐Rong Dong^²³, Ming‐Fang Zhao^¹⁶, Gui‐Bin Qiao^¹, Jiu‐Wei Cui^²⁴, Zi‐Ming Li^², Zhi‐Jie Wang^²⁵, Xiao‐Yuan Chen^²⁶, Nong Yang^²⁷, Gen Lin^⁸, Pan‐Wen Tian^⁴, Yun Fan^²⁸, Qi‐Bin Song^²⁹, Yuan Chen^³⁰, Jian‐Chun Duan^²⁵, Jia‐Lei Wang^²¹, Bo Zhu^³¹, Bu‐Hai Wang^³², Jun Zhao^¹⁹, Qi‐Tao Yu^³³, Li‐Feng Wang^³⁴, Hai‐Bo Zhang^³⁵, Jie Hu^³⁶, Rui Ma^³⁷, Tong‐Mei Zhang^³⁸, Jie Lin^³⁹, Qian Chu^³⁰, Sheng‐Xiang Ren^⁴⁰, Yu Yao^⁴¹, Lin Wu^²⁷, Hui‐Juan Wang^⁴², Fang Wu^⁴³, Wen‐Zhao Zhong^¹, Yi Hu^¹², Ke‐Neng Chen^¹⁹, Jian Zhao^⁴⁴, Li Zhang^⁴⁵, Fan Yang^⁴⁶, Qun Wang^³⁶, Dong‐Sheng Yue^⁴⁷, Jian‐Ya Zhou^⁷, Peng Shen^⁴⁸, Jia‐Tao Zhang^¹, Xiao‐Long Yan^⁴⁹, Mei‐Juan Huang^⁴, Wei‐Neng Feng^⁵⁰, Li Li^⁵¹, Chinese Association of Lung Cancer, Guangdong Association of Clinical Trials (GACT)/Chinese Thoracic Oncology Group (CTONG)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China

Jilin Cancer Hospital, Changchun, China

West China Hospital, Sichuan University, Chengdu, China

Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China

Sun Yat‐sen University Cancer Center, Guangzhou, China

The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

FuJian Cancer Hospital, Fuzhou, China

Xiangya Hospital of Central South University, Changsha, China

Burning Rock Biotech Co., Ltd., Guangzhou, China

Nanjing Geneseeq Technology Inc., Nanjing, China

Chinese PLA General Hospital, Beijing, China

The First Affiliated Hospital of Dalian Medical University, Dalian, China

Wuxi Genecast Biotechnology Co., Ltd., Wuxi, China

Shanghai Tongshu Biotechnology Co., Ltd., Shanghai, China

The First Hospital of China Medical University, Shenyang, China

The Second Affiliated Hospital of Nanchang University, Nanchang, China

Beijing GenePlus Technology Co., Ltd., Beijing, China

Beijing Cancer Hospital, Beijing, China

The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Fudan University Shanghai Cancer Center, Shanghai, China

General Hospital of Eastern Theater Command, Nanjing, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

The First Bethune Hospital of Jilin University, Changchun, China

Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China

School of Medicine, Tsinghua University, Beijing, China

Hunan Cancer Hospital, Changsha, China

Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China

Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China

Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China

Xinqiao Hospital, Army Medical University, Chongqing, China

Subei People's Hospital Affiliated to Nanjing Medical University, Yangzhou, China

Guangxi Medical University Cancer Hospital, Nanning, China

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

Zhongshan Hospital, Fudan University, Shanghai, China

Liaoning Cancer Hospital & Institute, Shenyang, China

Beijing Chest Hospital, Capital Medical University, Beijing, China

The Second Affiliated Hospital of Kunming Medical University, Kunming, China

Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

He'nan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

The Second Xiangya Hospital of Central South University, Changsha, China

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China

Peking Union Medical College Hospital, Beijing, China

Peking University People's Hospital, Beijing, China

Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

Nanfang Hospital, Guangzhou, China

Tangdu Hospital, Air Force Military Medical University, Xi'an, China

The First People's Hospital of Foshan, Foshan, China

Daping Hospital of Army Medical University, Chongqing, China

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Abstract

The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.